Many diseases are caused by or associated with biomolecules, and it is useful to develop disease treatments, therapies, diagnostic reagents, and research reagents that target biomolecules and, optionally, modulate their activities. Agents, including therapeutic, diagnostic, and research agents, that bind to more than one site may be desired, so that a single molecule can bind either to multiple regions of the same target biomolecule, or else to multiple different targets. The approach described herein provides novel bispecific bivalent binding proteins based on a unique core structure which may be adapted to generate binding proteins that bind additional epitopes (i.e., have additional specificities) e.g. trispecific binding proteins, tetraspecific binding proteins, pentaspecific binding proteins.